Throughout this application various publications are referred to in superscript. Full citations for these references may be found at the end of the specification. The disclosures of these publications are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Many pharmacotherapeutic compounds or their metabolites are electron-deficient species (electrophiles) that cause toxicity through chemical modification of functionally important proteins. For example, although at therapeutic doses, acetaminophen (paracetamol, N-acetyl-p-aminophenol; AAP) is a safe and effective antipyretic/analgesic, AAP overdose produces severe hepatotoxicity in humans and laboratory animals characterized by centrilobular necrosis. In the U.S., AAP overdose is the leading cause of drug-induced liver failure requiring transplantation67.
The present invention addresses the need for improved methods and compositions for treating and preventing toxicity that can be associated with administration of therapeutic agents or agents that cause oxidative cellular damage to subjects.